Mucopolysaccharidosis I

MPS I

Mucopolysaccharidosis Type I (MPS I), also known as Hurler (severe MPS I), Scheie, and Hurler-Scheie (attenuated / less severe MPS I) syndrome is part of a group of rare lysosomal storage diseases (LSD) caused by reduced levels, or the complete lack of, an enzyme responsible for the catabolism (break down) of glycosaminoglycans (GAGs) and resulting in the progressive accumulation of GAGs in the tissue. 1

GAG accumulation has a direct effect on connective tissue formation and function, causing progressive cellular damage affecting multiple organ systems and can lead to organ failure, cognitive impairment and reduced life expectancy.1

People with severe MPS I typically have an earlier onset of symptoms, a decline in intellectual function, and without treatment individuals with severe MPS I typically die before 10 years of age.1

Attenuated MPS I typically has a later onset of symptoms, milder symptoms and slower disease progression. While individuals with attenuated MPS I may develop significant disease-related morbidity, they typically show normal intelligence and may survive into adulthood.1

Heart disease and airway obstruction are major causes of death in all people with MPS I.2

Current standard of care for MPS includes haematopoietic stem cell transplantation (HSCT) and/or disease modifying enzyme replacement therapy (ERT), or supportive medical and surgical interventions.3

Despite available therapies people with MPS diseases continue to experience bone and joint manifestations, chronic pain, and physical disability, which generally persist despite treatment with HSCT and ERT.3

MPS I is present in about 1 in every 100,000 live births.4

Mucopolysaccharidosis I

MPS I

Mucopolysaccharidosis Type I (MPS I), also known as Hurler (severe MPS I), Scheie, and Hurler-Scheie (attenuated / less severe MPS I) syndrome is part of a group of rare lysosomal storage diseases (LSD) caused by reduced levels, or the complete lack of, an enzyme responsible for the catabolism (break down) of glycosaminoglycans (GAGs) and resulting in the progressive accumulation of GAGs in the tissue. 1

GAG accumulation has a direct effect on connective tissue formation and function, causing progressive cellular damage affecting multiple organ systems and can lead to organ failure, cognitive impairment and reduced life expectancy.1

People with severe MPS I typically have an earlier onset of symptoms, a decline in intellectual function, and without treatment individuals with severe MPS I typically die before 10 years of age.1

Attenuated MPS I typically has a later onset of symptoms, milder symptoms and slower disease progression. While individuals with attenuated MPS I may develop significant disease-related morbidity, they typically show normal intelligence and may survive into adulthood.1

Heart disease and airway obstruction are major causes of death in all people with MPS I.2

Current standard of care for MPS includes haematopoietic stem cell transplantation (HSCT) and/or disease modifying enzyme replacement therapy (ERT), or supportive medical and surgical interventions.3

Despite available therapies people with MPS diseases continue to experience bone and joint manifestations, chronic pain, and physical disability, which generally persist despite treatment with HSCT and ERT.3

MPS I is present in about 1 in every 100,000 live births.4

Key MPS I Figures

Incidence of live births4
1/100K
Expected lifespan with severe form, untreated1
10 YRS
Expected lifespan with attenuated form1
50 YRS
Market size (USD/pa) by 20275
$828M+

Key MPS I Figures

Incidence of live births4
1/100K
Expected lifespan with severe form, untreated1
10 YRS
Expected lifespan with attenuated form1
50 YRS
Market size (USD/pa) by 20275
$828M+

Drug in development

Pentosan
Polysulfate
Sodium

for subcutaneous injection

Potential

There is an unmet need to help manage bone and joint manifestations, chronic pain, and physical disability, key clinical manifestations of MPS I which remain despite treatment with HSCT and ERT.3
PPS has been shown to reduce GAG levels, inflammatory biomarkers, joint stiffness, and pain in preclinical MPS models and in clinical trials in MPS patients.6-10

The mechanisms of action of PPS that are relevant to the treatment of MPS include:

- Reduction in systemic and accumulated GAGs in multiple tissues11
- Anti-inflammatory effects via the inhibition of NF-kB resulting in the reduction in pro-inflammatory mediators12
- Reduction of the expression of the pain mediator, nerve growth factor (NGF) in osteocytes from degenerating joints 13
- An ability to inhibit the cartilage degrading enzymes that are related to joint dysfunction observed in MPS14

Remodelling
Inflammation
Pain
Cartilage Loss

Development milestones

In 2018, Paradigm entered into an exclusive license agreement for the use of PPS to treat lysosomal storage diseases (LSDs) including MPS (MPS types I, II, III, IV, VI and VII), Gaucher and Fabry diseases. The licensing agreement is a valuable addition to Paradigm’s product pipelines and IP portfolio. Granted patents cover key regions such as USA, Japan, Europe, Australia and New Zealand.

Paradigm is interested in exploring strategic partnerships to progress clinical studies to further evaluate PPS as a treatment to address the critical unmet need of ongoing musculoskeletal symptoms in this very rare patient population.

Mucopolysaccharidosis I

MPS I

Mucopolysaccharidosis Type I (MPS I), also known as Hurler (severe MPS I), Scheie, and Hurler-Scheie (attenuated / less severe MPS I) syndrome is part of a group of rare lysosomal storage diseases (LSD) caused by reduced levels, or the complete lack of, an enzyme responsible for the catabolism (break down) of glycosaminoglycans (GAGs) and resulting in the progressive accumulation of GAGs in the tissue. 1

GAG accumulation has a direct effect on connective tissue formation and function, causing progressive cellular damage affecting multiple organ systems and can lead to organ failure, cognitive impairment and reduced life expectancy.1

People with severe MPS I typically have an earlier onset of symptoms, a decline in intellectual function, and without treatment individuals with severe MPS I typically die before 10 years of age.1

Attenuated MPS I typically has a later onset of symptoms, milder symptoms and slower disease progression. While individuals with attenuated MPS I may develop significant disease-related morbidity, they typically show normal intelligence and may survive into adulthood.1

Heart disease and airway obstruction are major causes of death in all people with MPS I.2

Current standard of care for MPS includes haematopoietic stem cell transplantation (HSCT) and/or disease modifying enzyme replacement therapy (ERT), or supportive medical and surgical interventions.3

Despite available therapies people with MPS diseases continue to experience bone and joint manifestations, chronic pain, and physical disability, which generally persist despite treatment with HSCT and ERT.3

MPS I is present in about 1 in every 100,000 live births.4

Mucopolysaccharidosis I

MPS I

Mucopolysaccharidosis Type I (MPS I), also known as Hurler (severe MPS I), Scheie, and Hurler-Scheie (attenuated / less severe MPS I) syndrome is part of a group of rare lysosomal storage diseases (LSD) caused by reduced levels, or the complete lack of, an enzyme responsible for the catabolism (break down) of glycosaminoglycans (GAGs) and resulting in the progressive accumulation of GAGs in the tissue. 1

GAG accumulation has a direct effect on connective tissue formation and function, causing progressive cellular damage affecting multiple organ systems and can lead to organ failure, cognitive impairment and reduced life expectancy.1

People with severe MPS I typically have an earlier onset of symptoms, a decline in intellectual function, and without treatment individuals with severe MPS I typically die before 10 years of age.1

Attenuated MPS I typically has a later onset of symptoms, milder symptoms and slower disease progression. While individuals with attenuated MPS I may develop significant disease-related morbidity, they typically show normal intelligence and may survive into adulthood.1

Heart disease and airway obstruction are major causes of death in all people with MPS I.2

Current standard of care for MPS includes haematopoietic stem cell transplantation (HSCT) and/or disease modifying enzyme replacement therapy (ERT), or supportive medical and surgical interventions.3

Despite available therapies people with MPS diseases continue to experience bone and joint manifestations, chronic pain, and physical disability, which generally persist despite treatment with HSCT and ERT.3

MPS I is present in about 1 in every 100,000 live births.4

Key MPS I Figures

Incidence of live births4
1/100K
Expected lifespan with severe form, untreated1
10 YRS
Expected lifespan with attenuated form1
50 YRS
Market size (USD/pa) by 20275
$828M+

Key MPS I Figures

Incidence of live births4
1/100K
Expected lifespan with severe form, untreated1
10 YRS
Expected lifespan with attenuated form1
50 YRS
Market size (USD/pa) by 20275
$828M+

Drug in development

Pentosan
Polysulfate
Sodium

for subcutaneous injection

Potential

There is an unmet need to help manage bone and joint manifestations, chronic pain, and physical disability, key clinical manifestations of MPS I which remain despite treatment with HSCT and ERT.3
PPS has been shown to reduce GAG levels, inflammatory biomarkers, joint stiffness, and pain in preclinical MPS models and in clinical trials in MPS patients.6-10

The mechanisms of action of PPS that are relevant to the treatment of MPS include:

- Reduction in systemic and accumulated GAGs in multiple tissues11
- Anti-inflammatory effects via the inhibition of NF-kB resulting in the reduction in pro-inflammatory mediators12
- Reduction of the expression of the pain mediator, nerve growth factor (NGF) in osteocytes from degenerating joints 13
- An ability to inhibit the cartilage degrading enzymes that are related to joint dysfunction observed in MPS14

Remodelling
Inflammation
Pain
Cartilage Loss

Development milestones

In 2018, Paradigm entered into an exclusive license agreement for the use of PPS to treat lysosomal storage diseases (LSDs) including MPS (MPS types I, II, III, IV, VI and VII), Gaucher and Fabry diseases. The licensing agreement is a valuable addition to Paradigm’s product pipelines and IP portfolio. Granted patents cover key regions such as USA, Japan, Europe, Australia and New Zealand.

Paradigm is interested in exploring strategic partnerships to progress clinical studies to further evaluate PPS as a treatment to address the critical unmet need of ongoing musculoskeletal symptoms in this very rare patient population.